Regulation of Enzymes in Glycolysis and Gluconeogenesis

Question 1

PDH Kinase

Answer 1

+ ATP, Acetyl-Coa, NADH (indicates high energy in the cell to deactivate PDH complex so acetyl-CoA is not produced.

• Pyruvate (needs to be converted to acetyl-CoA)

Question 2

PDH Phosphatase

Answer 2

+ Ca2+ (indicates contracting muscle and a need for energy, so acetyl-CoA is needed.

Removes phosphate group from PDH complex

Question 3

Pyruvate dehydrogenase complex

Answer 3

• by its own products, NADH and acetyl-CoA

Question 4

PFK-2

Answer 4

Increase in BG levels = + INSULIN, which - cAMP, which - protein kinase, which dephosphorylates the bifunctional enzyme, activating PFK-2 activity, leading to production of F 2,6-bisphosphate and increase glycolysis

Question 5

Fructose 2,6-bisphosphatase

Answer 5

Decrease in BG levels = + GLUCAGON, which + cAMP, which + Protein kinase, which phosphorylates the enzyme, activating F 2,6-bisphosphatase leading to the production of F-6-phosphate and a decrease in glycolysis

Question 6

PFK-1

Answer 6

• ATP, Citrate

+ AMP, Fructose 2,6-bisphosphate

RATE-LIMITING STEP

Question 7

Hexokinase

Answer 7

• Glucose-6-phosphate (its own product)

*low Km for glucose

Question 8

Glucokinase

Answer 8

• F-6-P

+ F-1-P

*Liver only
**INDUCIBLE enzyme + INSULIN

***High Km for glucose

Question 9

Pyruvate kinase

Answer 9

1. ALLOSTERIC
   + F 1,6-bisphosphate (product of gatekeeper step) to + cAMP + protein kinase, and phosphorylation
2. COVALENT MODULATION via glucagon signaling
3. INDUCTION (in the LIVER) by a combination of high CHO diet and high insulin levels

Question 10

Fructose 1,6-bisphosphatase

Answer 10

• F 2,6-bisP
• AMP

Question 11

PEPCK

Answer 11

long-term hormonal regulation + GLUCAGON = increase synthesis of PEPCK

Question 12

Glucose-6-phosphatase

Answer 12

Long-term hormonal regulation + GLUCAGON = increase synthesis of itself

*Liver only

Question 13

Citrate Synthase

Answer 13

• ATP

Primary regulation is the availability of its substrates (Acetyl-CoA and OAA)

Question 14

Isocitrate dehydrogenase

Answer 14

• ATP, NADH

+ ADP, AMP, Ca2+

Question 15

Alpha-ketoglutarate dehydrogenase complex

Answer 15

• ATP, GTP, NADH, Succinyl-CoA (its own product)

+ Ca2+

Question 16

Pyruvate carboxylase

Answer 16

+ [acetyl-CoA in mito] due to FA oxidation

*ANAPLEROTIC REACTION (chemical reaction that forms intermediates of metabolic pathways).

Question 17

Protein kinase

Answer 17

• INSULIN

+ GLUCAGON

Question 18

How is the activity of the bifunctional enzyme different in the liver and heart?

Answer 18

HEART: Phosphorylation by PROTEIN KINASE occurs at a different site that +s rather than inhibits PFK-2. This produces an INCREASE rather than a decrease in F 2,6-bisP levels (which results in an increase in PFK-2 and INCREASED GLYCOLYSIS.

LIVER: the opposite of above

Question 19

How is gluconeogenesis allosterically regulated?

Answer 19

FA OXIDATION promotes gluconeogenesis and inhibits glycolysis by: causing an INCREASE in acetyl-CoA in mito which:
a. + Pyruvate carboxylase
b. + Citrate (- effect on PFK-1 which decreases F 1,6-bisP, that - pyruvate kinase)
c. - AMP

Question 20

How does glucagon and insulin regulate gluconeogenesis covalently and through induction?

Answer 20

+ Glucagon via covalent modulation regulates in the SHORT-TERM by glucagon: + cAMP, which + protein kinase, causing phosphorylation of the bifunctional enzyme, which - F 2,6-bisP favoring gluconeogenesis.

+ Glucagon in the LONG-TERM causes induction and increase synthesis of PEPCK and Glucose-6-phosphatase while decreasing synthesis of Glucokinase and Pyruvate kinase.